PURPOSE: To study the topography of photoreceptor loss early in the course of Leber congenital amaurosis (LCA) caused by RPE65 mutations. METHODS: Young patients with RPE65-LCA (n = 9; ages, 6-17 years) were studied with optical coherence tomography (OCT) in a wide region of central retina. Outer nuclear layer (ONL) thickness was mapped topographically and compared with that in normal subjects and in older patients with RPE65-LCA. RESULTS: Photoreceptor layer topography was abnormal in all young patients with RPE65-LCA. Foveal and extrafoveal ONL was reduced in most patients. There were interindividual differences, with ONL thicknesses at most retinal locations ranging from near the detectability limit to a significant fraction of normal. These differences were not clearly related to age. In most patients, there was a thinner ONL inferior to the fovea compared with that in the superior retina. Summary maps obtained by aligning and averaging photoreceptor topography across all young patients showed a relative preservation of ONL in the superior-temporal and temporal pericentral retina. These retinal regions also showed the greatest magnitude of interindividual variation. CONCLUSIONS: Photoreceptor loss in the foveal and extrafoveal retina was prominent, even in the youngest patients studied. Differences in the topography of residual photoreceptors in children with RPE65-LCA suggest that it may be advisable to use individualized ONL mapping to guide the location of subretinal injections for gene therapy and thereby maximize the potential for efficacy.
PURPOSE: To study the topography of photoreceptor loss early in the course of Leber congenital amaurosis (LCA) caused by RPE65 mutations. METHODS: Young patients with RPE65-LCA (n = 9; ages, 6-17 years) were studied with optical coherence tomography (OCT) in a wide region of central retina. Outer nuclear layer (ONL) thickness was mapped topographically and compared with that in normal subjects and in older patients with RPE65-LCA. RESULTS: Photoreceptor layer topography was abnormal in all young patients with RPE65-LCA. Foveal and extrafoveal ONL was reduced in most patients. There were interindividual differences, with ONL thicknesses at most retinal locations ranging from near the detectability limit to a significant fraction of normal. These differences were not clearly related to age. In most patients, there was a thinner ONL inferior to the fovea compared with that in the superior retina. Summary maps obtained by aligning and averaging photoreceptor topography across all young patients showed a relative preservation of ONL in the superior-temporal and temporal pericentral retina. These retinal regions also showed the greatest magnitude of interindividual variation. CONCLUSIONS: Photoreceptor loss in the foveal and extrafoveal retina was prominent, even in the youngest patients studied. Differences in the topography of residual photoreceptors in children with RPE65-LCA suggest that it may be advisable to use individualized ONL mapping to guide the location of subretinal injections for gene therapy and thereby maximize the potential for efficacy.
Authors: G M Acland; G D Aguirre; J Ray; Q Zhang; T S Aleman; A V Cideciyan; S E Pearce-Kelling; V Anand; Y Zeng; A M Maguire; S G Jacobson; W W Hauswirth; J Bennett Journal: Nat Genet Date: 2001-05 Impact factor: 38.330
Authors: Samuel G Jacobson; Gregory M Acland; Gustavo D Aguirre; Tomas S Aleman; Sharon B Schwartz; Artur V Cideciyan; Caroline J Zeiss; Andras M Komaromy; Shalesh Kaushal; Alejandro J Roman; Elizabeth A M Windsor; Alexander Sumaroka; Susan E Pearce-Kelling; Thomas J Conlon; Vincent A Chiodo; Sanford L Boye; Terence R Flotte; Albert M Maguire; Jean Bennett; William W Hauswirth Journal: Mol Ther Date: 2006-04-27 Impact factor: 11.454
Authors: Daniel Barthelmes; Florian K Sutter; Malaika M Kurz-Levin; Martina M Bosch; Horst Helbig; Günter Niemeyer; Johannes C Fleischhauer Journal: Invest Ophthalmol Vis Sci Date: 2006-03 Impact factor: 4.799
Authors: Y Huang; A V Cideciyan; G I Papastergiou; E Banin; S L Semple-Rowland; A H Milam; S G Jacobson Journal: Invest Ophthalmol Vis Sci Date: 1998-11 Impact factor: 4.799
Authors: Vera L Bonilha; Mary E Rayborn; Yong Li; Gregory H Grossman; Eliot L Berson; Joe G Hollyfield Journal: Invest Ophthalmol Vis Sci Date: 2011-10-28 Impact factor: 4.799
Authors: J Pang; S E Boye; B Lei; S L Boye; D Everhart; R Ryals; Y Umino; B Rohrer; J Alexander; J Li; X Dai; Q Li; B Chang; R Barlow; W W Hauswirth Journal: Gene Ther Date: 2010-03-18 Impact factor: 5.250
Authors: Samuel G Jacobson; Artur V Cideciyan; Alejandro J Roman; Alexander Sumaroka; Sharon B Schwartz; Elise Heon; William W Hauswirth Journal: N Engl J Med Date: 2015-05-03 Impact factor: 91.245
Authors: Stephen H Tsang; Lawrence Chan; Yi-Ting Tsai; Wen-Hsuan Wu; Chun-Wei Hsu; Jin Yang; Joaquin Tosi; Katherine J Wert; Richard J Davis; Vinit B Mahajan Journal: Trans Am Ophthalmol Soc Date: 2014-07
Authors: Artur V Cideciyan; Tomas S Aleman; Sanford L Boye; Sharon B Schwartz; Shalesh Kaushal; Alejandro J Roman; Ji-Jing Pang; Alexander Sumaroka; Elizabeth A M Windsor; James M Wilson; Terence R Flotte; Gerald A Fishman; Elise Heon; Edwin M Stone; Barry J Byrne; Samuel G Jacobson; William W Hauswirth Journal: Proc Natl Acad Sci U S A Date: 2008-09-22 Impact factor: 11.205
Authors: Edwin M Stone; Artur V Cideciyan; Tomas S Aleman; Todd E Scheetz; Alexander Sumaroka; Mary A Ehlinger; Sharon B Schwartz; Gerald A Fishman; Elias I Traboulsi; Byron L Lam; Anne B Fulton; Robert F Mullins; Val C Sheffield; Samuel G Jacobson Journal: Arch Ophthalmol Date: 2011-01
Authors: Samuel G Jacobson; Artur V Cideciyan; Ramakrishna Ratnakaram; Elise Heon; Sharon B Schwartz; Alejandro J Roman; Marc C Peden; Tomas S Aleman; Sanford L Boye; Alexander Sumaroka; Thomas J Conlon; Roberto Calcedo; Ji-Jing Pang; Kirsten E Erger; Melani B Olivares; Cristina L Mullins; Malgorzata Swider; Shalesh Kaushal; William J Feuer; Alessandro Iannaccone; Gerald A Fishman; Edwin M Stone; Barry J Byrne; William W Hauswirth Journal: Arch Ophthalmol Date: 2011-09-12
Authors: Sirichai Pasadhika; Gerald A Fishman; Edwin M Stone; Martin Lindeman; Ruth Zelkha; Irma Lopez; Robert K Koenekoop; Mahnaz Shahidi Journal: Invest Ophthalmol Vis Sci Date: 2009-12-03 Impact factor: 4.799